Salivary miR-31-5p, miR-345-3p, and miR-424-3p Are Reliable Biomarkers in Patients with Oral Squamous Cell Carcinoma.

If not detected early, oral squamous cell carcinoma (OSCC) has very poor prognosis, emphasizing the need for reliable early diagnostics. Saliva is considered a promising surrogate biosample for OSCC detection, because it comes into contact with many cells of the tumor mass, providing a comprehensive sampling of tumor-specific biomolecules. Although several protein- and RNA-based salivary biomarkers have been proposed for the detection of OSCC, the results of the studies show large differences. Our goal was to clarify which salivary microRNAs (miRNA) show reliably high expression in the saliva of OSCC patients, to be used as cancer-specific biomarkers, and potentially as early diagnostic biomarkers. Based on a detailed literature search, we selected six miRNAs commonly overexpressed in OSCC, and analyzed their expression in saliva samples of cancer patients and controls by real-time quantitative PCR. Our results suggest that miR-345 and miR-31-5p are consistently upregulated salivary biomarkers for OSCC, and a three-miRNA panel of miR-345, miR-31-5p, and miR-424-3p can distinguish cancer and control patients with high sensitivity.

Oral health-related quality of life after prosthetic rehabilitation: a longitudinal study with the OHIP questionnaire.

BACKGROUND: Aspects of oral health related quality of life (OHRQoL) attracted an increased attention recently. OBJECTIVE: The aim of the study was to assess self-reported oral health related quality of life (OHRQoL) among patients requiring prosthetic rehabilitation and to determine the rate of improvement 1 month and 6-12 months after therapy. In addition, effect of age, gender, oral health indicators and denture types before treatment were assessed on OHRQoL as evaluated and reported by the patients. METHODS: Hungarian version of OHIP-49 (OHIP-49-H) questionnaire was completed before oral rehabilitation (T0-phase) by 389 patients undergoing prosthetic replacement. After 1 month (T1-phase) and 6-12 months (T2-phase) recall periods 235 and 92 patients completed the questionnaire. The median interquartile range (IQR) values of the total OHIP-49-H score were calculated for T0-, T1- and T2-phases. Reliability of the questionnaire was checked by Cronbach's statistics. Age, gender, oral health indicators and denture types of patients before and after treatment were recorded and treatment-associated changes in OHRQoL were evaluated. RESULTS: The study demonstrated the excellent reliability and internal consistency of OHIP-49-H by a high and narrow range of Cronbach's alpha value (0.81-0.93). A median OHIP-49-H score of 52; IQR = 25-83 demonstrated a poor OHRQoL on first admission. Decreasing median total OHIP-49-H scores 1 month (24; IQR = 9-51; p < 0.001) and 6-12 months (20; IQR = 7-37; p = 0,055) after therapy indicated an improvement of OHRQoL. Patients' age and CPI value assessed before treatment proved to be significant factors of OHRQoL. CONCLUSIONS: Here we presented representative data about self-assessed OHRQoL of patients requiring prosthetic treatment from Hungary using OHIP-49-H questionnaire. The results demonstrated that the restoration of oral health was associated with an improvement in patients' OHRQoL. According to the demographical and T0 phase clinical status, the treatment was more effective in the respect of OHIP-49-H score improvement among females (than among males), among younger (than among more aged), and among patients with more serious CPI assessed at T0. The type of prosthetic interventions did not exert a significant effect on total OHIP-49-H score, suggesting that the improvement in OHRQoL is independent from the type of denture applied.

Overlapping protective and destructive regulatory pathways in apical periodontitis.

INTRODUCTION: Protective and destructive immunoreactions take place simultaneously in apical periodontitis. However, the same reactions defending the periapical area from infection-derived damage may also result in host tissue injury. METHODS: The inflammatory reaction of the periapical tissues is self-limited. Regeneration of the injured tooth-supporting structures may follow elimination of the causative microbial irritation. RESULTS: Recent experimental and clinical observations have identified important interplay between positive and negative regulatory pathways. A network of stimulatory and inhibitory feedback loops may influence the intensity of the defense and inflammatory responses and the balance between bone resorption and regeneration, resulting in lesion expansion or healing of apical periodontitis. CONCLUSIONS: We critically discuss research data on regulatory mechanisms that control the activity of host effector cells and signaling molecules during interactions with pathogenic microbes.

Oral cancer report from Northeastern Hungary.

In Hungary oral and pharyngeal cancers have been reported the fourth most common malignancy in males and the sixth for both sexes. The aim of the present study was to characterize oral squamous cell carcinoma (OSCC) patients in Northeastern Hungary. 119 randomly selected patients with OSCC were included in the study. Epidemiological data, clinicopathological parameters and the risk factors were registered. The most common sites of OSCC were the floor of the mouth (27.7%), the lip (26.9%) and the tongue (22.7%). The majority of the patients was diagnosed with early stage (I-II) lesions and moderately differentiated tumors. The 5-year overall survival rate was 38.7%. There was a significant correlation between survival and tumor size, lymph node involvement and clinical stage. At the time of diagnosis 65.5% of the patients were smokers. Smoking significantly correlated with younger age, male gender, advanced clinical stages and alcohol consumption. 75.5% of the patients consumed alcohol, 41.1% of them exceeding the conventional amount regularly. Drinking habit significantly correlated with younger age, male gender and tumor site i.e. gingiva, retromolar region, tongue. The dental status was acceptable only in 12.6% of the cases. There was a significant correlation between dental status and age, smoking and drinking habits. Clinical stage has the most significant impact on survival and the most important high-risk habits in Northeastern Hungary are smoking and alcohol consumption. Therefore, early detection and treatment, cessation of tobacco and alcohol abuse, and a regular dental care may improve patients' survival in the region.

Oral and dental conditions of children with selective IgA deficiency.

Oral conditions in selective IgA deficiency in children have rarely been published. Our aims were to investigate their mucosal, periodontal, and cariological conditions in IgA deficient children matched with healthy controls and to draw data on their oral health in the North-East Region of Hungary. Thirty four patients and 111 healthy controls, matched by age and sex, were studied for oral mucosal disorders, periodontal disease, and caries. Mucosal diseases were found in 10 (29%) patients. The severity of periodontal lesions characterized by plaque index, gingival index and pocket depth (exceeding more than 3 mms) was similar in patients and controls. A significant difference was observed in caries experience of the primary, but not in the permanent dentition as assessed by the dmf/DMF-t/T; s/S system used universally to quantitate decayed, missing, and filled teeth and tooth surfaces both in primary (small letters) and in permanent (capital letters) dentitions. Patients with IgA deficiency had significantly higher dmft, and dmfs indices than controls, supporting the notion that children with selective IgA deficiency exhibit an increased risk for developing dental caries. However the severities of mucosal or periodontal disorders are comparable with that in the normal population.

The influence of chronic apical periodontitis on oral and general health.

In healthy condition, the periodontal space between the root surface and the alveolar bone is relatively poor in cells. In case of root canal infection however, large number of immune-inflammatory cells infiltrate the periapical region of the affected teeth. A major issue is if and to what extent microbial and host cells contribute to lesion formation and whether the local inflammation may impair general health. The question is important as it may fundamentally influence the therapeutic strategy in patients with apical periodontitis. The aim of this paper is to review the results of recent experimental and clinical observations that investigate the importance of cellular interactions in exerting protective and destructive effects in periapical inflammatory lesions. The majority of studies indicate that the lesion would not develop in the absence of permanent release of bacteria and their by-products from the infected root canal. On the other hand, the formation of the classical granulation tissue is dependent on the presence and proper function of host cells and regulatory molecules. The dynamic encounter of root canal microbiota and the local immune system prevents overwhelming bacterial infiltration of the periradicular space but it is also connected with degenerative changes, most importantly bone resorption, resulting ultimately in tooth loss. However, by the use of proper endodontic methods, the lesion can be successfully treated in the majority of cases. Remineralization of the lost hard tissue will occur or the lesion will transform into an inert periapical scar.

Expression of p16(INK4A), p53, and Rb proteins are independent from the presence of human papillomavirus genes in oral squamous cell carcinoma.

BACKGROUND: The overexpression of p16(INK4A) and suppression of p53 and Rb proteins are key features of oncogenic transformation by human papillomaviruses (HPV) in anogenital cancers. HPV genomes are often detected in cancers of the oral cavity, but it is unclear whether HPV has a specific oncogenic role there. OBJECTIVES: The objectives of the study were to investigate the expression of p53, Rb, and p16(INK4A) proteins and identify HPV infection and viral integration into the host genome. METHODS: Seventy-nine cases of oral squamous cell carcinoma (OSCC) were studied by immunohistochemistry. Polymerase chain reaction (PCR) was performed to identify HPV DNA from the samples. The results were correlated with clinical data. RESULTS: Thirty-three cases were HPV positive for high-risk HPV (HR-HPV) types, of which 27 harbored HPV16. In 25 of 27 HPV16-positive tumors, the HPV16 genome was fully integrated into the host genome, as evidenced by the lack of PCR-amplifiable E2 gene sequences. Forty-five patients were p53 overexpressing, 20 with HR-HPV-positive and 25 with HR-HPV-negative tumors. p16(INK4A) protein was overexpressed in 4 of 31 HR-HPV-positive and 9of 45 HR-HPV-negative cases. Twenty-six of 32 HR-HPV-positive and 37 of 44 HR-HPV-negative samples exhibited pRb nuclear staining. These differences between HR-HPV-positive and -negative tumors were not statistically significant. No correlation was found between these biological factors and tumor location, stage, differentiation grade, or alcohol or tobacco abuse. CONCLUSIONS: A tumor immunophenotype, similar to HPV-related anogenital cancers, is not present in OSCC and highly oncogenic HPV types are therefore unlikely to be specific or independent risk factors for oral cancer.

p21WAF1/CIP1 expression is a marker of poor prognosis in oral squamous cell carcinoma.

BACKGROUND: Previous research on the prognostic relevance of p21(WAF1/CIP1) in oral squamous cell carcinomas (OSCC) yielded inconclusive and contradictory data. OBJECTIVES: To investigate the prognostic significance of p21(WAF1/CIP1) expression, its relationship to p53 accumulation, proliferation-associated proteins Ki-67 and cyclin D1 in relation to survival and clinicopathological features in OSCC. METHODS: Surgical specimens taken from 106 randomly selected patients were studied by immunohistochemistry. Expression of the protein of interest was correlated with clinical data. RESULTS: p21(WAF1/CIP1) expression was found in 61.3% of OSCCs. Expression of p21(WAF1/CIP1) significantly correlated with tumor size (P = 0.005), lymph node involvement (P = 0.002), clinical stage (P < 0.001), and tumor site (P = 0.002). Patients with tumors showing p21(WAF1/CIP1) immunopositivity had decreased 2-year survival (P = 0.018). Expression of p21(WAF1/CIP1) was not related to age, gender, risk factors (tobacco, alcohol), dental status, or tumor differentiation grade. The p21(WAF1/CIP1) expression positively correlated with proliferation-related variables Ki-67 (P = 0.010) and cyclin D1 (P < 0.001), but not with p53 expression. CONCLUSIONS: The expression of p21(WAF1/CIP1) was found to be associated with poorer prognosis and tumor aggressivity in OSCC.